Our long-term goal is to understand brain mechanisms of hearing. The building blocks for this goal will be to determine the neural circuitry established by auditory nerve fibers in the cochlear nucleus, to describe the development of this circuitry, and to identify the role of hearing on this development. The cochlear nucleus is the focus of this research because it is the terminus of the auditory nerve that conveys all known acoustic information to the brain. In addition, the cochlear nucleus gives rise to all ascending auditory pathways. How the brain processes sound will be heavily dependent upon the organization of auditory nerve input. Intracellular recording and staining methods will be used to label the myelinated auditory nerve fibers in cats. The staining of single fibers after first characterizing their physiological response properties will permit us to make direct comparisons between a fiber's response features, its synaptic morphology, and its connections with neurons of the cochlear nucleus. By combining single fiber staining with other pathway tracing techniques and immunocytochemical methods, we can determine the organization of auditory nerve input at the single neuron level using light and electron microscopy. Some of the pathology of congenital deafness in adult cat brains has already been described. We will examine how congenital deafness affects synaptic organization and development, and we will determine to what extent cochlear implants prevent or reverse deafness-related abnormalities. We will begin searching for the gene(s) that cause deafness in our colony of deaf white cats. Studies of synaptic development in congenitally deaf mice are underway to verify the generality of results in cats. The proposed research will address the organization of auditory nerve projections to the cochlear nucleus, explore synaptic development and plasticity with respect to deafness and hearing restoration, and begin work on genes and congenital deafness. These results will be relevant to issues surrounding cochlear implants in children by defining the time period during which the developing auditory nervous system is most vulnerable to acoustic deprivation, and should advance our understanding of principles of sensory neurobiology.